Background: Primary pulmonary hypertension (PPH) is progressive, resulting in right ventricular failure. Survival seldom exceeds five years. Pulmonary hypertension can be idiopathic or associated with other conditions. It is common in patients with diffuse scleroderma and the CREST syndrome where it is clinically, haemodynamically and prognostically indistinguishable from idiopathic primary pulmonary hypertension. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. Iloprost is a chemically stable derivative of prostacyclin with similar biologic properties and can be given orally, by infusion or nebulised.
Objectives: To determine the efficacy of prostacyclin or one of its analogues in idiopathic primary pulmonary hypertension.
Search strategy: A search was carried out using the Cochrane controlled clinical trial register.
Selection criteria: Randomised controlled trials (RCTs) involving patients with primary pulmonary hypertension were selected by two reviewers.
Data collection and analysis: Study quality was assessed and data extracted independently by two reviewers. Outcomes were analysed as continuous and dichotomous outcomes, using standard statistical techniques.
Main results: Four RCTs were included, all of short duration (8-12 weeks). Three compared intravenous epoprostenol with conventional therapy, two were in PPH (n = 81 and n = 21) and one with pulmonary hypertension in scleroderma (n = 111). One compared intravenous Iloprost with placebo in 14 patients with scleroderma. Exercise capacity improved in patients treated with intravenous epoprostenol (Standardised Mean Difference) 0.69, 95% Confidence Intervals (CI) 0.40, 0.97. Several haemodynamic variables improved in the group treated with epoprostenol; e.g. mean pulmonary artery pressure fell: Weighted Mean Difference -6.3 mmHg (95% CI -3.9, -8.7). Mortality was improved Peto Odds Ratio 0.32 (95% CI 0.13, 0.77), although this effect was not significant when analysed using a more conservative random effects model: Odds Ratio 0.32 (95% CI 0.06, 1.58). Side effects and adverse events related to the indwelling catheter (sepsis and thrombosis) were common.
Reviewer's conclusions: Intravenous prostacyclin over 12 weeks improves exercise capacity, NYHA functional class and several cardiopulmonary haemodynamic variables. It may improve mortality.